Maleimides are considered to be high performance reactive monomers. The most useful members of this family are the bismaleimides (i.e., reactive monomers containing two maleimide functional groups per molecule). The maleimide function is very reactive and can be cured homogeneously via free radical or anionic mechanisms to yield a polymer linked through succinimide residues. The maleimide group is also a potent dienophile and is capable of reacting via a Diel's Alder mechanism with suitable dienes (or diene precursors such as benzocyclobutenes) to yield polymeric materials. The carbon-carbon double bond in the maleimide group is considered to be very electron deficient and has been observed to form perfectly alternating copolymers via a charge transfer mechanism with electron rich monomers (e.g., cyclo-olefins and vinyl ethers). Furthermore, aliphatic maleimide compounds have recently been shown to be capable of uncatalyzed photopolymerization. Finally, the maleimide group is a very useful reactant in the "ene reaction" and thus bismaleimdes can be used as vulcanizing agents for polyunsaturated polyolefins and rubbers.
The synthesis of maleimide compounds is typically accomplished in two steps. The first step involves the generation of an N-substituted maleamic acid by the direct reaction of a primary amine and maleic anhydride. The second step is the cyclodehydration of the maleamic acid to form the maleimide functional group. The overall scheme for the preparation of maleimide compounds is shown in scheme 1. ##STR1##
The formation of the maleamic acid is very facile and can usually be accomplished in quantitative yield. It is advisable, however, that the amine be slowly added to a solution containing a stoichiometric excess of the maleic anhydride (this precaution avoids the potential "Michael addition" of the amine across the carbon-carbon double bond of the maleamic acid).
Cyclodehydration of maleamic acid can be accomplished in a number of ways. For example, the use of a chemical dehydrating agent, such as acetic anhydride in the presence of sodium acetate, has been a well established method for accomplishing this second synthetic step (see, for example, U.S. Pat. No. 2,444,536). This method has been acceptable for the generation of technical grade versions of many aromatic maleimide compounds. It fails, however, when applied to the preparation of aliphatic maleimide compounds, and is not preferred for the preparation of high purity aromatic maleimides.
Another chemical dehydrating agent, N,N'-Dicyclohexylcarbodiimide (DCC), in combination with an isomerizing alcohol, has been used to effect cyclodehydration of amic acids to maleimides (see Martin, et al., U.S. Statutory Invention Registration H424, 1988). This method can be used to efficiently make both aliphatic and aromatic maleimides. Unfortunately, the DCC dehydrating agent is very expensive and is also a severe contact allergen for human skin.
Direct thermal cyclodehydration of maleamic acid can be accomplished by heating to a temperature in the neighborhood of 200EC. Unfortunately, this approach is impractical because polymerization of the resulting maleimide would be impossible to avoid under such extreme conditions. Thermal cyclodehydration can be accomplished at lower temperatures by the use of azeotropic distillation in the presence of an acid catalyst. The use of an azeotropic solvent permits the efficient removal of the water co-product as it forms, thereby driving the reaction toward the desired maleimide.
Suitable azeotropic solvents include cyclohexane, benzene, toluene, ethylbenzene, xylenes, cumene, chlorobenzene, butylbenzene, diethylbenzene, mesitylene, and the like. Toluene is considered to be the most desirable of these since it boils at 110EC at atmospheric pressure and is generally an adequate solvent for the amic acid at reflux temperatures. Cylcohexane, as well as the other aliphatic solvents mentioned above, are all much weaker solvents and are usually incapable of dissolving the amic acid. Benzene, which has a lower boiling point than toluene, is considered to be a human carcinogen and is therefore undesirable in any industrial process. The other aromatic solvents noted above have higher normal-atmospheric-pressure boiling points than toluene and thus might be expected to allow for reduced reaction times. However, the higher boiling points of these solvents also can promote thermal isomerization of the maleamic acid to the more thermodynamically stable trans (fumaramic acid) structure, as shown in scheme 2. ##STR2## Dehydration of the fumaramic acid to a polyamide, instead of the desired maleimide, represents a serious side reaction that limits the usefulness of the higher boiling azeotropic solvents (see, for example Coleman, et al., Journal of Organic Chemistry, 24:135 (1959)). It would, of course, be possible to use any of the higher boiling solvents as a reaction medium under diminished pressure in order to conduct the reaction at a lower temperature.
Even with the use of toluene as the azeotropic dehydration solvent, poor yields and impractically long reaction times typically result. A significant improvement in both the yield and reaction time can be realized by the incorporation of a polar, aprotic solvent into the reaction mixture. Several polar, aprotic solvents, including dimethylformamide, dimethylacetamide, acetonitrile, N-methylpyrrolidone, dimethylsulfoxide and sulfolane have been claimed to be useful (see, for example, U.S. Pat. Nos. 5,484,948 and 5,371,236, incorporated herein by reference). The most useful of the polar, aprotic solvents is dimethylformamide. Presumably, the presence of the polar aprotic solvent facilitates the reaction by increasing the polarity of the reaction medium. The maleimides of both aromatic and aliphatic amines can be obtained in good yield through the use of these polar, aprotic co-solvents in combination with an azeotropic solvent.
The use of polar aprotic co-solvents does, however, present some problems. These solvents are completely miscible with the azeotropic solvents, making them difficult to remove from the reaction mixture. In addition, polar aprotic solvents generally have high boiling points, requiring higher temperatures and longer evaporation times (than would be required for the azeotropic solvent by itself) for complete removal during work-up of the maleimide product. An exception, acetonitrile, which does have a low boiling point, is impractical because it co-distills without phase separating from the water generated by the dehydration reaction, and cannot therefore remain in the reaction mixture throughout the process. The use of longer and higher temperature evaporation conditions increases the risk of polymerization of the maleimide product.
Polar, aprotic solvents could be removed through aqueous washings, but doing so would create a hazardous and potentially environmentally damaging waste stream. The polar, aprotic solvents, in addition to their own inherent toxicity, are noted for their ability to carry toxic solutes directly into the bloodstream upon contact with human skin. Furthermore, dimethylformamide and dimethylacetamide are subject to hydrolysis and are therefore partially destroyed during the cyclodehydration reaction.
There is, therefore, a need in the art for a viable substitute for the polar, aprotic solvent-containing media used in the thermal cyclodehydration of maleamic acids for the synthesis of maleimides. This and other needs are addressed by the present invention, as will become apparent to those of skill in the art upon review of the specification and appended claims.